SAR1A regulates the RhoA/YAP and autophagy signaling pathways to influence osteosarcoma invasion and metastasis.

Zhan, Fangbiao; Deng, Qianrong; Chen, Zhiyu; Xie, Chaozheng; Xiang, Shuang; Qiu, Sheng; Tian, Lin; Wu, Chunrong; Ou, Yunsheng; Chen, Jian; Xu, Lixin

Zhan, Fangbiao; Deng, Qianrong; Chen, Zhiyu; Xie, Chaozheng; Xiang, Shuang; Qiu, Sheng; Tian, Lin; Wu, Chunrong; Ou, Yunsheng; Chen, Jian; Xu, Lixin.

Afiliación

Zhan F; Department of Orthopedics, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing Municipality Clinical Research Center for Geriatric Diseases, Chongqing, China.
Deng Q; Orthopedic Laboratory of Chongqing Medical University, Chongqing, China.
Chen Z; Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xie C; Health Management Center, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, China.
Xiang S; Orthopedic Laboratory of Chongqing Medical University, Chongqing, China.
Qiu S; Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Tian L; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wu C; Department of Pathology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, China.
Ou Y; Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Chen J; Department of Clinical Laboratory, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, China.
Xu L; Department of Oncology, Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, China.

Cancer Sci ; 113(12): 4104-4119, 2022 Dec.

Article en En | MEDLINE | ID: mdl-36047971

RESUMEN

Osteosarcoma is the most prevalent form of primary bone malignancy affecting adolescents. Secretion-associated Ras-related GTPase 1A (SAR1A) is a key regulator of endoplasmic reticulum (ER) homeostasis, but its role as a regulator of osteosarcoma metastasis has yet to be clarified. Bioinformatics analyses revealed SAR1A and RHOA to be upregulated in osteosarcoma patients, with the upregulation of these genes being associated with poor 5-year metastasis-free survival rates. In addition, the upregulation of SAR1A and RHOA in osteosarcoma was highly positively correlated. Immunohistochemical analyses additionally revealed that SAR1A levels were increased in osteosarcoma pulmonary metastases. In vitro wound healing and Transwell assays indicated that knocking down SAR1A or RHOA impaired the invasive and migratory activity of osteosarcoma cells, whereas RHOA overexpression had the opposite effect. Western blotting and immunofluorescent staining revealed the inhibition of osteosarcoma cell epithelial-mesenchymal transition following SAR1A or RHOA knockdown; RHOA overexpression had the opposite effect. Following SAR1A knockdown, phalloidin staining indicated that osteosarcoma cells showed reduced lamellipodia formation. Endoplasmic reticulum stress levels and reactive oxygen species production were enhanced following the knockdown of SAR1A, as was autophagic activity, with lung metastases being reduced in vivo after such knockdown. Knocking down SAR1A suppresses osteosarcoma cell metastasis through the RhoA/YAP, ER stress, and autophagic pathways, offering new insights into the regulation of autophagic activity in the context of osteosarcoma cell metastasis and suggesting that these pathways could be amenable to therapeutic intervention.

Asunto(s)

Neoplasias Óseas; Neoplasias Pulmonares; Proteínas de Unión al GTP Monoméricas; Osteosarcoma; Adolescente; Humanos; Proteínas ras/metabolismo; Proliferación Celular; Línea Celular Tumoral; Osteosarcoma/patología; Neoplasias Óseas/patología; Autofagia/genética; Transducción de Señal; Neoplasias Pulmonares/genética; Neoplasias Pulmonares/secundario; Movimiento Celular/genética; Proteína de Unión al GTP rhoA/genética; Proteína de Unión al GTP rhoA/metabolismo; Proteínas de Unión al GTP Monoméricas/metabolismo

Palabras clave

ER stress; RhoA/YAP; SAR1A; autophagy; metastasis

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Osteosarcoma / Proteínas de Unión al GTP Monoméricas / Neoplasias Pulmonares Límite: Adolescent / Humans Idioma: En Revista: Cancer Sci Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

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